Clonal strains of the rat medullary thyroid carcinoma cell lines rMTC 44-2 and 6-23 were established by two different techniques which were designed to ensure that cells originated from single cells. These studies demonstrate that single cells are capable of producing both calcitonin (CT) and NT and that these strains are useful models for studies relating to the biosynthesis and secretory interrelationships of CT and NT. Ultrastructurally, the murine medullary thyroid carcinoma cells contain, in addition to membrane bound dense-core granules, intracisternal type A retrovirus particles. Preliminary evidence suggests they may be particularly valuable in the study of the secretory interrelationships of somatostatin and CT. Recent studies reporting thyroglobulin (TGB) immunoreactivity in normal and neoplastic C cells have raised a number of questions regarding the interrelationships of TGB and CT in these cells and the histogenesis of medullary thyroid carcinoma (MTC). Although results of the study do not completely exclude the possibility of TGB synthesis by MTC cells, they suggest that TGB immunoreactivity in MTC results primarily from entrapment and phagocytosis of TGB. In studies on long-term effects of dexamethasone and nerve growth factor (NGF) on adrenal medullary cells cultured from young adult rats, the human and rat pheochromocytoma cells show extensive NGF-induced process outgrowth in culture. Such outgrowth also occurs in cultures of normal adult human and neonatal rat chromaffin cells and is diminished in these cultures of normal cells by the corticosteroid dexamethasone. Ten human neuroblastomas were quantitatively evaluated for NGF responsiveness in primary cultures. There was no apparent correlation between survival and the presence of fluorescence, and cultures without NGF contained rare surviving fluorescent and non-fluorescent cells in approximately the same proportion as cultures with NGF. Specific goals for the coming year include preparation of dispersed cell cultures of normal and hyperplastic C cells from our aging-rat model system and study of their characteristics in short-term culture.